TÓPICOS SELECTOS DE DISEÑO I

CRITERIOS DE DISEÑO DE
BIOPROCESOS
 BIOPROCESO
MATERIAS PRIMAS

CIP
PROCESOS
UPSTREAM

CIP y FORMULACIÓN DE
PREPARACIÓN DE ESTERILIZACION DE
MEDIO Y
CIP INÓCULO EQUIPO
ESTERILIZACIÓN
CIP y
EIP
BIORREACTOR -
FERMENTADOR
AIRE DE
PROCESO
EIP

FENÓMENOS DE
CINËTICAS DE
TRANSPORTE Y INSTRUMENTACIÓN Y
REACCIÓN Y
PROPIEDADES DE CONTROL
BIOACTIVIDAD
LOS FLUIDOS

CIP
PROCESOS
DOWNSTREAM

RECUPERACIÓN DE
RECUPERACIÓN Y
SEPARACIÓN DESPERDICIOS Y
PURIFICACIÓN
REUSO

CIP
TYPICAL BIOPROCESS FLOW
SHEET
PREPARATION
OF BIOMASS
Innoculum Stages
FOAM CONTROL
Antifoam Addition
pH CONTROL
Acid-Alkali Addition

PRODUCT RECOVERY

CELL SEPARATION
BIOREACTOR Intracellular
product
Extracellular
1). CELL DISTRUPTION product
2). PRODUCT EXTRACTION

Free Cells,
Immoblized Cells PRODUCT
or CONCENTRATION
PROCESS
Enzyme Bioreactor

PRODUCT
SEPARATION

PURIFICATION

STERILIZATION
DRYING

RAW MATERIAS Air FINAL PRODUCT

Nutrients and Reactants
in Aqueous Solution
(may contain insoluble
organic and/or inorganic
materials)
TABLE 1. Basic Bioreactor Design Criteria
___________________________________________________________________
 Microbiological and Biochemical Characteristics
of the Cell System (Microbial, Mammalian,
Plant)
 Hydrodynamic Characteristics of the bioreactor
 Mass and Heat Transfer Characteristics of the
Bioreactor
 Kinetics of the Cell Growth and Product
Formation
 Genetic Stability Characteristics of the Cell
System
 Aseptic Equipment Design
 Control of Bioreactor Environment (both macro-
and micro-environment)
 Implications of Bioreactor Design on
Downstream Products Separation
 Capital and Operating Costs of the Bioreactor
 Potential for Bioreactor Scale-up
______________________________________________________________________
 Fermenter Design
• The basic points of consideration while designing a fermentor:
• · Productivity and yield
• · Fermenter operability and reliability
• · Product purification
• · Water management
• · Energy requirements
• · Waste treatment
• Other few significant things to be taken in account:
• · Design in features so that process control will be possible over
reasonable ranges of process variables.
• · Operation should be reliable
• · Operation should be contamination free
 Fermenter design
• To achieve these the fermenter should have:
• · Heat and oxygen transfer configuration
• · Sterilization procedures
• · Foam control
• · Fast and thorough cleaning system
• · Proper monitoring and control system
• Traditional design is open cylindrical or rectangular vessels made
from wood or stone.
• Most fermentations are now performed in close system to avoid
contamination.
• It should be constructed from non-toxic, corrosion-resistant
materials.
• Small fermentation vessels of a few liters capacity are constructed
from glass and/or stainless steel.
 Fermenter design
• Pilot scale and many production vessels are normally made of
stainless steel with polished internal surfaces
• Very large fermenters are often constructed from mild steel lined
with glass or plastic, in order to reduce the cost.
• If aseptic operation is required, all associated pipelines transporting
air, inoculum and nutrients for the fermentation need to be
sterilizable, usually by steam.
• Most vessel cleaning operations are now automated using spray jets,
and called cleaning in place CIP. And located within the vessel.
• Associated pipe work must also be designed to reduce the risk of
microbial contamination. There should be no horizontal pipes or
unnecessary joints and dead stagnant spaces where material can
accumulate; otherwise this may lead to ineffective sterilization.
 4.2.2 Basic features of a stirred tank bioreactor; Oxygen
delivery system - Air sterilization system

• Sterilization of the inlet air is undertaken to prevent contaminating

organisms from entering the reactor.
• The exit air on the other hand is sterilized not only to keep
contaminants from entering but also to prevent organisms in the
reactor from contaminating the air.
• A common method of sterilising the inlet and exit air is filtration.
For small reactors (with volumes less than 5 litres), disk shaped
hydrophobic Teflon membranes housed in a polypropylene housing
is used. are used. Teflon is tough, reusable and does not readily
block.
 Sterilisation of the air

For larger laboratory scale fermenters (up to 1000 litres), pleated membrane filters
housed in polypropylene cartridges are used.
 Sterilisation of the air

• By pleating the membrane, it is possible to create a compact filter with a very

large surface area for air filtration. Increasing the filtration area decreases the
pressure required to pass a given volume of air through the filter.
• Sterilization of the inlet and exit air in large bioreactors (> 10,000 litres) can
present a major design problem. Large scale membrane filtration is a very
expensive process. The filters are expensive as they are difficult to make and
the energy required to pass air through a filter can be quite considerable.
• Heat sterilization is alternative option. Steam can be used to sterilize the air.
With older style compressors, it was possible to use the heat generated by
the air compression process to sterilize the air. However, compressors are
now multi-stage devices which are cooled at each stage and disinfecting
temperatures are never reached.
 4.2.3 Basic features of a STR
Oxygen delivery system
Air sterilisation system - Positive pressure

• During sterilisation the concept of "maintaining positive pressure" will often be

used.
• Maintaining positive pressure means that during sterilisation, cooling and filling
and if appropriate, the fermentation process, air must be pumped into the
reactor.
• In this way the reactor is always pressurised and thus aerial contaminants will
not be "sucked" into the reactor.
• It is very important that positive pressure is maintained when the bioreactor is
cooled following sterilisation. Without air being continuously pumped into the
reactor, a vacuum will form and contaminants will tend to be drawn into the
reactor.
 Air sterilisation system -
Positive pressure
Maintaining positive pressure at all stages of the fermentation setup and operation
is an important aspect of reducing the risk of contamination

Without aeration, a vacuum With aeration, positive pressure is

always maintained and contaminants
forms as the reactor cools.
are pushed away from the reactor